Publications by authors named "Kenji Hayashi"

87 Publications

The role of early visual experience in the development of spatial-frequency preference in the primary visual cortex.

J Physiol 2021 Sep 13;599(17):4131-4152. Epub 2021 Aug 13.

Division of Visual Information Processing, National Institute for Physiological Sciences, National Institutes of Natural Sciences, Okazaki, Japan.

Key Points: The mature functioning of the primary visual cortex depends on postnatal visual experience, while the orientation/direction preference is established just after eye-opening, independently of visual experience. In this study, we find that visual experience is required for the normal development of spatial-frequency (SF) preference in mouse primary visual cortex. We show that age- and experience-dependent shifts in optimal SFs towards higher frequencies occurred similarly in excitatory neurons and parvalbumin-positive interneurons. We also show that some excitatory and parvalbumin-positive neurons preferentially responded to visual stimuli consisting of very high SFs and posterior directions, and that the preference was established at earlier developmental stages than the SF preference in the standard frequency range. These results suggest that early visual experience is required for the development of SF representation and shed light on the experience-dependent developmental mechanisms underlying visual cortical functions.

Abstract: Early visual experience is crucial for the maturation of visual cortical functions. It has been demonstrated that the orientation and direction preferences in individual neurons of the primary visual cortex are well established immediately after eye-opening. The postnatal development of spatial frequency (SF) tuning and its dependence on visual experience, however, has not been thoroughly quantified. In this study, macroscopic imaging with flavoprotein autofluorescence revealed that the optimal SFs shift towards higher frequency values during normal development in mouse primary visual cortex. This developmental shift was impaired by binocular deprivation during the sensitive period, postnatal 3 weeks (PW3) to PW6. Furthermore, two-photon Ca imaging revealed that the developmental shift of the optimal SFs, depending on visual experience, concurrently occurs in excitatory neurons and parvalbumin-positive inhibitory interneurons (PV neurons). In addition, some excitatory and PV neurons exhibited a preference for visual stimuli consisting of particularly high SFs and posterior directions at relatively early developmental stages; this preference was not affected by binocular deprivation. Thus, there may be two distinct developmental mechanisms for the establishment of SF preference depending on the frequency values. After PW3, SF tuning for neurons tuned to standard frequency ranges was sharper in excitatory neurons and slightly broader in PV neurons, leading to considerably attenuated SF tuning in PV neurons compared to excitatory neurons by PW5. Our findings suggest that early visual experience is far more important than orientation/direction selectivity for the development of the neural representation of the diverse SFs.
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http://dx.doi.org/10.1113/JP281463DOI Listing
September 2021

Failure patterns after adjuvant chemoradiotherapy following endoscopic resection for superficial esophageal squamous cell carcinoma.

Cancer Med 2019 08 20;8(10):4547-4554. Epub 2019 Jun 20.

Department of Radiation Oncology, Osaka International Cancer Institute, Osaka, Japan.

Background: This study evaluated the locations of lymph node recurrence and their association with irradiation fields used for radiotherapy after adjuvant chemoradiotherapy following endoscopic resection for superficial esophageal squamous cell carcinoma.

Methods: Medical records of 96 consecutive patients with superficial esophageal squamous cell carcinoma who underwent adjuvant chemoradiotherapy following endoscopic resection were reviewed. Computed tomography was used to identify whether nodal recurrences were within the elective nodal irradiation field. The cumulative incidence of recurrence was calculated, accounting for death as a competing risk. Univariate and multivariate analyses identified factors predicting nodal recurrence.

Results: The median follow-up period was 61 months (range: 6-137 months). Seven patients (7.3%) developed lymph node recurrence only; two patients (2.1%) developed nodal plus local recurrence. Six of the seven cases without local recurrence involved the elective nodal irradiation field, with five cases involving the recurrent nerve lymph nodes. The 5-year cumulative incidence of lymph node recurrence was higher for T1b tumors with lymphovascular invasion than for T1a tumors with lymphovascular invasion (17.6% vs 6.2%, P = 0.086; HR: 3.74, 95% CI: 0.80-17.52, P = 0.094) and T1b tumors without lymphovascular invasion (17.6% vs 3.3%, P = 0.031; HR: 6.78, 95% CI: 0.80-57.63, P = 0.080).

Conclusions: Lymph node recurrence frequently involved the elective nodal irradiation field, with recurrent nerve lymph nodes being common metastasis sites. The high incidence of nodal recurrence for T1b tumors with lymphovascular invasion highlights a need for new strategies for treating this subset of superficial esophageal squamous cell carcinomas.
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http://dx.doi.org/10.1002/cam4.2365DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6712456PMC
August 2019

Second nationwide surveillance of bacterial pathogens in patients with acute uncomplicated cystitis conducted by Japanese Surveillance Committee from 2015 to 2016: antimicrobial susceptibility of Escherichia coli, Klebsiella pneumoniae, and Staphylococcus saprophyticus.

J Infect Chemother 2019 Jun 21;25(6):413-422. Epub 2019 Mar 21.

Kawahara Urology Clinic, Kagoshima, Japan.

The Japanese Surveillance Committee conducted a second nationwide surveillance of antimicrobial susceptibility patterns of uropathogens responsible for acute uncomplicated cystitis (AUC) in premenopausal patients aged 16-40 years old at 31 hospitals throughout Japan from March 2015 to February 2016. In this study, the susceptibility of causative bacteria (Escherichia coli, Klebsiella pneumoniae, Staphylococcus saprophyticus) for various antimicrobial agents was investigated by isolation and culturing of organisms obtained from urine samples. In total, 324 strains were isolated from 361 patients, including E. coli (n = 220, 67.9%), S. saprophyticus (n = 36, 11.1%), and K. pneumoniae (n = 7, 2.2%). The minimum inhibitory concentrations (MICs) of 20 antibacterial agents for these strains were determined according to the Clinical and Laboratory Standards Institute (CLSI) manual. At least 93% of the E. coli isolates showed susceptibility to fluoroquinolones and cephalosporins, whereas 100% of the S. saprophyticus isolates showed susceptibility to fluoroquinolones and aminoglycosides. The proportions of fluoroquinolone-resistant and extended-spectrum β-lactamase (ESBL)-producing E. coli strains were 6.4% (13/220) and 4.1% (9/220), respectively. The antimicrobial susceptibility of K. pneumoniae was retained during the surveillance period, while no multidrug-resistant strains were identified. In summary, antimicrobial susceptibility results of our second nationwide surveillance did not differ significantly from those of the first surveillance. Especially the numbers of fluoroquinolone-resistant and ESBL-producing E. coli strains were not increased in premenopausal patients with AUC in Japan.
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http://dx.doi.org/10.1016/j.jiac.2019.02.021DOI Listing
June 2019

Explaining the ocean's richest biodiversity hotspot and global patterns of fish diversity.

Proc Biol Sci 2018 10 10;285(1888). Epub 2018 Oct 10.

Department of Ecology and Evolutionary Biology, University of Arizona, Tucson, AZ 85721-0088, USA.

For most marine organisms, species richness peaks in the Central Indo-Pacific region and declines longitudinally, a striking pattern that remains poorly understood. Here, we used phylogenetic approaches to address the causes of richness patterns among global marine regions, comparing the relative importance of colonization time, number of colonization events, and diversification rates (speciation minus extinction). We estimated regional richness using distributional data for almost all percomorph fishes (17 435 species total, including approximately 72% of all marine fishes and approximately 33% of all freshwater fishes). The high diversity of the Central Indo-Pacific was explained by its colonization by many lineages 5.3-34 million years ago. These relatively old colonizations allowed more time for richness to build up through diversification compared to other warm-marine regions. Surprisingly, diversification rates were decoupled from marine richness patterns, with clades in low-richness cold-marine habitats having the highest rates. Unlike marine richness, freshwater diversity was largely derived from a few ancient colonizations, coupled with high diversification rates. Our results are congruent with the geological history of the marine tropics, and thus may apply to many other organisms. Beyond marine biogeography, we add to the growing number of cases where colonization and time-for-speciation explain large-scale richness patterns instead of diversification rates.
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http://dx.doi.org/10.1098/rspb.2018.1314DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6191688PMC
October 2018

[A Case of Malignant Peritoneal Mesothelioma Treated with Cisplatin and Pemetrexed].

Gan To Kagaku Ryoho 2018 Jun;45(6):993-995

Dept. of Gastroenterology, Iwamizawa Municipal General Hospital.

A 65-year-old man was admitted to our hospital complaining of general malaise, anorexia and weight loss. A computed tomography(CT)scan showed massive ascites and multiple peritoneal masses. Although adenocarcinoma was suspected based on the cytology of the ascites, we were unable to determine the site of origin. We next performed a laparoscopy and a biopsy of the tumor on the omentum. The laparoscopy showed small, white, hard nodules that were disseminated throughout the abdominalcavity, and histologicaldiagnosis confirmed malignant peritonealmesothel ioma. The patient was administered chemotherapeutic treatment of cisplatin and pemetrexed. After treatment, the ascites decreased; however, tumor regression was not observed. The patient's performance status gradually decreased, and he died on hospital day 104. Prognosis of malignant peritoneal mesothelioma remains poor, and malignant peritoneal mesothelioma should be considered when diagnosing peritoneal tumors.
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June 2018

MTCL1 plays an essential role in maintaining Purkinje neuron axon initial segment.

EMBO J 2017 05 10;36(9):1227-1242. Epub 2017 Mar 10.

Molecular Cellular Biology Laboratory, Yokohama City University Graduate School of Medical Life Science, Tsurumi-ku Yokohama, Japan

The axon initial segment (AIS) is a specialized domain essential for neuronal function, the formation of which begins with localization of an ankyrin-G (AnkG) scaffold. However, the mechanism directing and maintaining AnkG localization is largely unknown. In this study, we demonstrate that knockdown of microtubule cross-linking factor 1 (MTCL1) in cerebellar Purkinje cells causes loss of axonal polarity coupled with AnkG mislocalization. MTCL1 lacking MT-stabilizing activity failed to restore these defects, and stable MT bundles spanning the AIS were disorganized in knockdown cells. Interestingly, during early postnatal development, colocalization of MTCL1 with these stable MT bundles was observed prominently in the axon hillock and proximal axon. These results indicate that MTCL1-mediated formation of stable MT bundles is crucial for maintenance of AnkG localization. We also demonstrate that gene disruption results in abnormal motor coordination with Purkinje cell degeneration, and provide evidence suggesting possible involvement of MTCL1 dysfunction in the pathogenesis of spinocerebellar ataxia.
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http://dx.doi.org/10.15252/embj.201695630DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5412768PMC
May 2017

Relationship between white matter integrity and serum cortisol levels in drug-naive patients with major depressive disorder: diffusion tensor imaging study using tract-based spatial statistics.

Br J Psychiatry 2016 06 18;208(6):585-90. Epub 2016 Feb 18.

Xiaodan Liu, MD, Department of Radiology, University of Occupational and Environmental Health, Fukuoka, Japan, and Medical Imaging Center, 1st Affiliated Hospital of Jinan University, Guangzhou, China; Keita Watanabe, MD, Shingo Kakeda, MD, PhD, Department of Radiology, University of Occupational and Environmental Health, Fukuoka, Japan; Reiji Yoshimura, MD, PhD, Department of Psychiatry, University of Occupational and Environmental Health, Fukuoka, Japan; Osamu Abe, MD, PhD, Department of Radiology, Nihon University School of Medicine, Tokyo, Japan; Satoru Ide, MD, Department of Radiology, University of Occupational and Environmental Health, Fukuoka, Japan; Kenji Hayashi, MD, Asuka Katsuki, MD, Wakako Umene-Nakano, MD, PhD, Department of Psychiatry, University of Occupational and Environmental Health, Fukuoka, Japan; Rieko Watanabe, MD, Issei Ueda, MD, Department of Radiology, University of Occupational and Environmental Health, Fukuoka, Japan; Jun Nakamura, MD, PhD, Department of Psychiatry, University of Occupational and Environmental Health, Fukuoka, Japan; Yukunori Korogi, MD, PhD, Department of Radiology, University of Occupational and Environmental Health, Fukuoka, Japan.

Background: Higher daytime cortisol levels because of a hyperactive hypothalamic-pituitary-adrenal axis have been reported in patients with major depressive disorder (MDD). The elevated glucocorticoids inhibit the proliferation of the oligodendrocytes that are responsible for myelinating the axons of white matter fibre tracts.

Aims: To evaluate the relationship between white matter integrity and serum cortisol levels during a first depressive episode in drug-naive patients with MDD (MDD group) using a tract-based spatial statistics (TBSS) method.

Method: The MDD group (n = 29) and a healthy control group (n = 47) underwent diffusion tensor imaging (DTI) scans and an analysis was conducted using TBSS. Morning blood samples were obtained from both groups for cortisol measurement.

Results: Compared with the controls, the MDD group had significantly reduced fractional anisotropy values (P<0.05, family-wise error (FWE)-corrected) in the inferior fronto-occipital fasciculus, uncinate fasciculus and anterior thalamic radiation. The fractional anisotropy values of the inferior fronto-occipital fasciculus, uncinate fasciculus and anterior thalamic radiation had significantly negative correlations with the serum cortisol levels in the MDD group (P<0.05, FWE-corrected).

Conclusions: Our findings indicate that the elevated cortisol levels in the MDD group may injure the white matter integrity in the frontal-subcortical and frontal-limbic circuits.
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http://dx.doi.org/10.1192/bjp.bp.114.155689DOI Listing
June 2016

Genetic Variation in the Catechol-O-Methyl Transferase Val108/158Met Is Linked to the Caudate and Posterior Cingulate Cortex Volume in Healthy Subjects: Voxel-Based Morphometry Analysis of Brain Magnetic Resonance Imaging.

PLoS One 2015 13;10(11):e0142862. Epub 2015 Nov 13.

Department of Radiology, Nihon University School of Medicine, Tokyo, Japan.

The effect of the catechol-O-methyltransferase (COMT) Val158Met polymorphism on brain morphology has been investigated but remains controversial. We hypothesized that a comparison between Val/Val and Val/Met individuals, which may represent the most different combinations concerning the effects of the COMT genotype, may reveal new findings. We investigated the brain morphology using 3-Tesla magnetic resonance imaging in 27 Val/Val and 22 Val/Met individuals. Voxel-based morphometry revealed that the volumes of the bilateral caudate and posterior cingulate cortex were significantly smaller in Val/Val individuals than in Val/Met individuals [right caudate: false discovery rate (FDR)-corrected p = 0.048; left caudate: FDR-corrected p = 0.048; and bilateral posterior cingulate cortex: FDR-corrected p = 0.048]. This study demonstrates that interacting functional variants of COMT affect gray matter regional volumes in healthy subjects.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0142862PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4643939PMC
June 2016

RELATIONSHIP BETWEEN THE CORTICAL THICKNESS AND SERUM CORTISOL LEVELS IN DRUG-NAÏVE, FIRST-EPISODE PATIENTS WITH MAJOR DEPRESSIVE DISORDER: A SURFACE-BASED MORPHOMETRIC STUDY.

Depress Anxiety 2015 Sep 20;32(9):702-8. Epub 2015 Aug 20.

Department of Radiology, University of Occupational and Environmental Health, Fukuoka, Japan.

Objective: In major depressive disorder (MDD) patients, higher morning cortisol levels due to a hyperactive hypothalamic-pituitary-adrenal (HPA) axis have been reported. The aim of the present study was to evaluate the relationship between cortical thinning and the serum cortisol levels during the first depressive episode in drug-naïve MDD patients using an automated surface-based morphometry (SBM) method.

Methods: The institutional review board approved this prospective study. MR imaging data were obtained using a 3T scanner by a three-dimensional fast-spoiled gradient recalled acquisition with steady state (3D-FSPGR). Thirty drug-naïve patients with MDD and 41 age- and gender-matched healthy subjects (controls) were enrolled. We then used the SBM method (Freesurfer) to generate cortical thickness maps, and measured the cortical thickness in each subject. Morning blood samples were drawn from all participants for cortisol measurements.

Results: We found the serum cortisol levels were significantly higher in the MDD patients than in the controls. The MDD patients manifested significant thinning of the left lateral orbitofrontal cortex compared with the controls. There was a significant negative linear correlation between the thickness of the left lateral orbitofrontal cortex and the serum cortisol levels in the MDD patients.

Conclusions: In the early stage of MDD, the thickness of the lateral orbitofrontal cortex was significantly reduced, and also showed a significant inverse correlation with the serum cortisol levels. Since the lateral orbitofrontal cortex contains a high concentration of glucocorticoid receptor, glucocorticoid receptor-mediated signaling transductions could contribute to neurotoxicity, which might occur when there are high cortisol levels in patients with MDD.
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http://dx.doi.org/10.1002/da.22401DOI Listing
September 2015

Relationship between the catechol-O-methyl transferase Val108/158Met genotype and brain volume in treatment-naive major depressive disorder: Voxel-based morphometry analysis.

Psychiatry Res 2015 Sep 31;233(3):481-7. Epub 2015 Jul 31.

Department of Radiology, University of Occupational and Environmental Health, Fukuoka, Japan.

Catechol-O-methyltransferase (COMT) is a methylation enzyme engaged in the degradation of dopamine and noradrenaline by catalyzing the transfer of a methyl group from S-adenosylmethionine. An association was found between the Valine (Val) 108/158Methionine (Met) COMT polymorphism (rs4680) and major depressive disorder (MDD). The authors prospectively investigated the relationship between the Val108/158Met COMT genotype and voxel-based morphometry (VBM) findings for patients with first-episode and treatment-naïve MDD and healthy subjects (HS). Participants comprised 30 MDD patients and 48 age- and sex-matched HS who were divided according to the COMT genotype. Effects of diagnosis, COMT genotype, and the genotype-diagnosis interaction in relation to brain morphology in the Val/Met and Val/Val individuals were evaluated using a VBM analysis of high-resolution magnetic resonance imaging findings. Among the Val/Met individuals, the volume of the bilateral caudate was significantly smaller for MDD patients than for HS. In the Val/Val individuals, the caudate volume was comparable between MDD patients and HS. Significant genotype-diagnosis interaction effects on brain morphology were noted in the right caudate.
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http://dx.doi.org/10.1016/j.pscychresns.2015.07.024DOI Listing
September 2015

Relationship between a BDNF gene polymorphism and the brain volume in treatment-naive patients with major depressive disorder: A VBM analysis of brain MRI.

Psychiatry Res 2015 Aug 30;233(2):120-4. Epub 2015 May 30.

Department of Radiology, University of Occupational and Environmental Health, Japan.

The brain-derived neurotrophic factor (BDNF) relates to basic neuronal functions, such as cell survival, axonal outgrowth, and dendritic growth. The Val66Met polymorphism of the BDNF gene may affect genetic susceptibility to major depressive disorder (MDD). We prospectively investigated the relationship between the Val66Met BDNF genotype and voxel-based morphometry (VBM) findings for first episode and drug-naïve MDD patients and healthy subjects (HS). Participants comprised 38 MDD patients and 42 age- and sex-matched HS were divided into groups based on their BDNF genotype. The effects of diagnosis and genotype, as well as the genotype-diagnosis interaction, in relation to brain morphology were evaluated using a voxel-by-voxel statistical analysis of high-resolution magnetic resonance imaging (MRI) findings. Among the Met-carriers, the volume of the left middle frontal gyrus (composition of the prefrontal cortex [PFC]) was significantly smaller for MDD patients than for the HS, i.e., there was a significant genotype-diagnosis interaction effect on brain morphology noted in the left PFC. The BDNF polymorphism was associated with atrophy of the PFC in MDD patients, which suggests that the BDNF Val66Met polymorphism may play an important role in the pathogenesis of early stages of MDD.
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http://dx.doi.org/10.1016/j.pscychresns.2015.05.016DOI Listing
August 2015

Elevated levels of CYP94 family gene expression alleviate the jasmonate response and enhance salt tolerance in rice.

Plant Cell Physiol 2015 Apr 29;56(4):779-89. Epub 2015 Jan 29.

Bioscience and Biotechnology Center, Nagoya University, Chikusa, Nagoya, 464-8601 Japan

The plant hormone jasmonate and its conjugates (JAs) have important roles in growth control, leaf senescence and defense responses against insects and microbial attacks. JA biosynthesis is induced by several stresses, including mechanical wounding, pathogen attacks, drought and salinity stresses. However, the roles of JAs under abiotic stress conditions are unclear. Here we report that increased expression of the Cyt P450 family gene CYP94C2b enhanced viability of rice plants under saline conditions. This gene encodes an enzyme closely related to CYP94C1 that catalyzes conversion of bioactive jasmonate-isoleucine (JA-Ile) into 12OH-JA-Ile and 12COOH-JA-Ile. Inactivation of JA was facilitated in a rice line with enhanced CYP94C2b expression, and responses to exogenous JA and wounding were alleviated. Moreover, salt stress-induced leaf senescence but not natural senescence was delayed in the transgenic rice. These results suggest that bioactive JAs have a negative effect on viability under salt stress conditions and demonstrate that manipulating JA metabolism confers enhanced salt tolerance in rice.
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http://dx.doi.org/10.1093/pcp/pcv006DOI Listing
April 2015

MTCL1 crosslinks and stabilizes non-centrosomal microtubules on the Golgi membrane.

Nat Commun 2014 Nov 4;5:5266. Epub 2014 Nov 4.

Molecular Cellular Biology Laboratory, Yokohama City University, Graduate School of Medical Science, 1-7-29 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan.

Recent studies have revealed the presence of a microtubule subpopulation called Golgi-derived microtubules that support Golgi ribbon formation, which is required for maintaining polarized cell migration. CLASPs and AKAP450/CG-NAP are involved in their formation, but the underlying molecular mechanisms remain unclear. Here, we find that the microtubule-crosslinking protein, MTCL1, is recruited to the Golgi membranes through interactions with CLASPs and AKAP450/CG-NAP, and promotes microtubule growth from the Golgi membrane. Correspondingly, MTCL1 knockdown specifically impairs the formation of the stable perinuclear microtubule network to which the Golgi ribbon tethers and extends. Rescue experiments demonstrate that besides its crosslinking activity mediated by the N-terminal microtubule-binding region, the C-terminal microtubule-binding region plays essential roles in these MTCL1 functions through a novel microtubule-stabilizing activity. These results suggest that MTCL1 cooperates with CLASPs and AKAP450/CG-NAP in the formation of the Golgi-derived microtubules, and mediates their development into a stable microtubule network.
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http://dx.doi.org/10.1038/ncomms6266DOI Listing
November 2014

Sex differences in the prevalence, progression, and improvement of chronic kidney disease.

Kidney Blood Press Res 2014 23;39(4):279-88. Epub 2014 Aug 23.

International Kidney Evaluation Association Japan, #702 Ichigaya Linden Bldg., 3-25 Ichigayahonmura-cho, Shinjuku-ku, Japan.

Background/aims: We examined sex differences in prevalence, progression, and improvement in early-stage chronic kidney disease (CKD).

Methods: We analyzed data from 533 participants who took 4 consecutive annual CKD detection tests.

Results: Urine albumin-creatinine ratio (ACR), estimated glomerular filtration rate (eGFR), and hemoglobin (Hb) at baseline in men with and without CKD and in women with and without CKD were 8.3±6.1, 149.2±310.4, 10.2±5.8, and 96.7±246.8 mg/g Cr; 83.4±14.7, 63.8±18.8, 79.9±13.0, and 69.4±20.0 mL/min/1.73 m2; and 14.8±1.2, 14.3±1.4, 13.0±1.0, and 13.0±1.2 mg/dL, respectively. ACR levels decreased significantly over time in men and women with CKD and they increased significantly over time in men and women without CKD. eGFR levels in men and women with CKD did not significantly change over time, but they decreased significantly over time in men and women without CKD. CKD prevalence and progression rate were not significantly different between sexes. Among the CKD participants, significantly more women had a "cured" status at 3 years (39.1% vs. 19.4%, P<0.01). Most whose eGFR increased to >60 mL/min/1.73 m2 at 3 years had values just below those at baseline. Regression analysis showed that change in eGFR correlated significantly with ACR in men with CKD (change in eGFR = -1.707+0.022×ACR, P<0.001, r2=0.201) and with Hb and ACR in women with CKD (change in eGFR = 48.870-3.803×Hb + 0.018×ACR, P<0.05, r2=0.134).

Conclusions: These results suggest that the slight decrease of Hb within a normal range and mild anemia can be managed in women with early-stage CKD. The key baseline for eGFR is 60 mL/min/1.73 m2.
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http://dx.doi.org/10.1159/000355805DOI Listing
June 2015

COMT Val158Met, but not BDNF Val66Met, is associated with white matter abnormalities of the temporal lobe in patients with first-episode, treatment-naïve major depressive disorder: a diffusion tensor imaging study.

Neuropsychiatr Dis Treat 2014 25;10:1183-90. Epub 2014 Jun 25.

Department of Psychiatry, Japan.

We investigated the association between the Val158Met polymorphism of the catechol-O-methyltransferase (COMT) gene, the Val66Met polymorphism of the brain-derived neurotrophic factor (BDNF) gene, and white matter changes in patients with major depressive disorder (MDD) and healthy subjects using diffusion tensor imaging (DTI). We studied 30 patients with MDD (17 males and 13 females, with mean age ± standard deviation [SD] =44±12 years) and 30 sex- and age-matched healthy controls (17 males and 13 females, aged 44±13 years). Using DTI analysis with a tract-based spatial statistics (TBSS) approach, we investigated the differences in fractional anisotropy, radial diffusivity, and axial diffusivity distribution among the three groups (patients with the COMT gene Val158Met, those with the BDNF gene Val66Met, and the healthy subjects). In a voxel-wise-based group comparison, we found significant decreases in fractional anisotropy and axial diffusivity within the temporal lobe white matter in the Met-carriers with MDD compared with the controls (P<0.05). No correlations in fractional anisotropy, axial diffusivity, or radial diffusivity were observed between the MDD patients and the controls, either among those with the BDNF Val/Val genotype or among the BDNF Met-carriers. These results suggest an association between the COMT gene Val158Met and the white matter abnormalities found in the temporal lobe of patients with MDD.
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http://dx.doi.org/10.2147/NDT.S61275DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4079817PMC
July 2014

Epithelial protein lost in neoplasm modulates platelet-derived growth factor-mediated adhesion and motility of mesangial cells.

Kidney Int 2014 Sep 2;86(3):548-57. Epub 2014 Apr 2.

1] Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan [2] National Center for Child Health and Development, Tokyo, Japan.

Mesangial cell migration, regulated by several growth factors, is crucial after glomerulopathy and during glomerular development. Directional migration requires the establishment of a polarized cytoskeletal arrangement, a process regulated by coordinated actin dynamics and focal adhesion turnover at the peripheral ruffles in migrating cells. Here we found high expression of the actin cross-linking protein EPLIN (epithelial protein lost in neoplasm) in mesangial cells. EPLIN was localized in mesangial angles, which consist of actin-containing microfilaments extending underneath the capillary endothelium, where they attach to the glomerular basement membrane. In cultured mesangial cells, EPLIN was localized in peripheral actin bundles at focal adhesions and formed a protein complex with paxillin. The MEK-ERK (extracellular signal-regulated kinase) cascade regulated EPLIN-paxillin interaction and induced translocalization of EPLIN from focal adhesion sites to peripheral ruffles. Knockdown of EPLIN in mesangial cells enhanced platelet-derived growth factor-induced focal adhesion disassembly and cell migration. Furthermore, EPLIN expression was decreased in mesangial proliferative nephritis in rodents and humans in vivo. These results shed light on the coordinated actin remodeling in mesangial cells during restorative remodeling. Thus, changes in expression and localization of cytoskeletal regulators underlie phenotypic changes in mesangial cells in glomerulonephritis.
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http://dx.doi.org/10.1038/ki.2014.85DOI Listing
September 2014

Abnormal white matter integrity in the corpus callosum among smokers: tract-based spatial statistics.

PLoS One 2014 7;9(2):e87890. Epub 2014 Feb 7.

Department of Psychiatry, University of Occupational and Environmental Health, Kitakyushu, Japan.

In the present study, we aimed to investigate the difference in white matter between smokers and nonsmokers. In addition, we examined relationships between white matter integrity and nicotine dependence parameters in smoking subjects. Nineteen male smokers were enrolled in this study. Eighteen age-matched non-smokers with no current or past psychiatric history were included as controls. Diffusion tensor imaging scans were performed, and the analysis was conducted using a tract-based special statistics approach. Compared with nonsmokers, smokers exhibited a significant decrease in fractional anisotropy (FA) throughout the whole corpus callosum. There were no significant differences in radial diffusivity or axial diffusivity between the two groups. There was a significant negative correlation between FA in the whole corpus callosum and the amount of tobacco use (cigarettes/day; R = - 0.580, p = 0.023). These results suggest that the corpus callosum may be one of the key areas influenced by chronic smoking.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0087890PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3917830PMC
May 2015

Transcriptional analysis of genes encoding proteins significantly increased in Kitasatospora setae KM-6054(T) under submerged culture.

J Gen Appl Microbiol 2014 ;60(6):276-80

Kitasato Institute for Life Sciences, Kitasato University, Tokyo, Japan; Graduate School of Infection Control Sciences, Kitasato University, Tokyo, Japan.

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http://dx.doi.org/10.2323/jgam.60.276DOI Listing
August 2015

[Current situation and problems associated with inactivation of microorganisms in water using copper].

Nihon Koshu Eisei Zasshi 2013 Sep;60(9):579-85

National Institute of Public Health.

Objectives: The current situation and problems associated with inactivation of microorganisms in water using copper were elucidated.

Methods: A literature review was conducted regarding the history and mechanisms of inactivation technology using copper, the variety of microorganisms shown to be inactivated by these methods in previous experiments, and the efficacy of such technologies for the inactivation of microorganisms in water.

Results: The use of copper for inactivation of microorganisms has a long history. Although the use of copper was discontinued temporarily owing to the advent of antibiotics in the 1930s, the occurrence of antibiotic-resistant bacteria has resulted in the need for different approaches to control pathogenic microorganisms. One such alternative is the use of copper. Although the mechanisms underlying the efficacy of copper inactivation technology have not yet been elucidated in detail, it has been suggested that pathogenic bacteria are inactivated due to the toxicity of copper ions and strong oxidation effects of reactive oxygen species. Copper inactivation technology is effective against many pathogenic microorganisms that pose a risk to public health, such as Legionella pneumophila, Salmonella enterica, and Mycobacterium tuberculosis. In recent years, copper inactivation technology has been used in various water-related devices, especially water supply pipes in buildings. Previous studies have demonstrated that microorganisms can be sufficiently inactivated by copper even at concentrations below that specified in the Water Quality Standard for Drinking Water. However, some previous studies have indicated that the inactivation effect of copper is short-lived. Therefore, the development of techniques to maintain a long-term inactivation effect is a key concern. In addition, it has been reported that the use of copper pipes triggers chlorine decay and results in the formation of chlorine disinfection byproducts. Hence, further studies should aim at assessing the risks and benefits associated with the use of copper.

Conclusion: Although the practical issues regarding copper inactivation technology are persistent, this method has been demonstrated to be efficacious. Therefore, this technology could be expected to be used in many devices such as water supply systems in hospitals in the near future.
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September 2013

[Tracheal intubation using Airtraq optical laryngoscope in an adult patient with Goldenhar syndrome].

Masui 2013 Jul;62(7):867-9

Moka 321-4306 Department of Anesthesiology, Haga Red Cross Hospital, Moka 321-4306.

A 23-year-old woman with Goldenhar syndrome and conductive deafness was scheduled for tympanoplasty. Goldenhar syndrome is a developmental disorder characterized by ear malformation, mandibular hypoplasia, and vertebral anomalies. Furthermore, she had micrognathia, trismus, and mandibular hypoplasia. Awake taracheal intubation was attempted to prevent airway obstruction, because we had anticipated her difficult airway (micrognathia, trismus, and mandibular hypoplasia). The vocal cords were visualized with a Cormac and Lehane grade I, using the Airtraq optical laryngoscope Small (Size 2), under sedation. Then, an endotracheal tube was inserted after induction of general anesthesia. This is the first case report on the successful orotracheal intubation using Airtraq in an adult with Goldenhar syndrome.
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July 2013

Follow-up Study on Electroconvulsive Therapy in Treatment-resistant Depressed Patients after Remission: A Chart Review.

Clin Psychopharmacol Neurosci 2013 Apr 24;11(1):34-8. Epub 2013 Apr 24.

Department of Psychiatry, School of Medicine, University of Occupational and Environmental Health, Fukuoka, Japan.

Objective: Electroconvulsive therapy (ECT) has proven to be effective in treatment-resistant depression (TRD). In recent reports, 70% to 90% of patients with TRD responded to ECT. However, post-ECT relapse is a significant problem. There are no studies investigating risk factors associated with reintroducing ECT in depressive patients after remission previously achieved with former ECT. The aim of the present study is to examine such risk factors using a sample of TRD patients.

Methods: We conducted a chart review to examine patient outcomes and adverse events over short- and long-term periods. Forty-two patients met the criteria for major depressive disorder.

Results: The response rate was 85.7% (36/42). There were no significant differences in the baseline characteristics of patients exhibiting remission, response or non-response. The rate of adverse events was 21.4% (9/42). Among 34 patients who were available for follow-up, 18 patients relapsed (relapse rate, 52.9%), and 6 patients were reintroduced to ECT. The patients' age and age of onset were significantly higher in the re-ECT group than non re-ECT group.

Conclusion: Our results suggest that older age and older age of onset might be considered for requirement of re-ECT after remission previously achieved with former ECT.
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http://dx.doi.org/10.9758/cpn.2013.11.1.34DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3650296PMC
April 2013

Current smoking rate in patients with psychiatric disorders in Japan: questionnaire survey.

Psychiatry Res 2013 Nov 17;210(1):268-73. Epub 2013 Apr 17.

Department of Psychiatry, School of Medicine, University of Occupational and Environmental Health, Japan. Electronic address:

The association between smoking and psychiatric disorders (PD) has been known for many years. Support for smoking cessation among patients with PD is provided in advanced nations, but there is a little support for smoking cessation among patients with PD in Japan, where few studies have investigated the smoking rate. The aim of the present study is to determine the smoking rate and smoking habits of Japanese patients with PD. The subjects included outpatients who visited the outpatient psychiatric clinic at a University hospital between January and March of 2011. They answered a questionnaire consisting of questions about their sociodemographic background and smoking habits. In an analysis of 733 subjects, the overall smoking rate was 25.1%. The smoking rates among the patients with schizophrenia and depression were 17.3% and 23.9%, respectively, and these rates were lower than the results of previous studies. Among the current smokers, 43.4% had experienced smoking cessation, and only 26.1% were not interested in smoking cessation. Of the current smokers, 37.5% spent between US$128.88 and US$257 per month on cigarettes.
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http://dx.doi.org/10.1016/j.psychres.2013.03.024DOI Listing
November 2013

No Association between the Response to the Addition of an Atypical Antipsychotic Drug to an SSRI or SNRI and the BDNF (Val66Met) Polymorphism in Refractory Major Depressive Disorder in Japanese Patients.

Clin Psychopharmacol Neurosci 2012 Apr 30;10(1):49-53. Epub 2012 Apr 30.

Department of Psychiatry, University of Occupational and Environmental Health, Kitakyushu, Japan.

Objective: This study examined the association between the brain-derived neurotrophic factor (BDNF) (Val66Met) polymorphism and the response to the addition of an atypical antipsychotic drug to a selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) in treatment-refractory depression.

Methods: The study enrolled 64 patients meeting the Diagnostic and Statistical Manual of Mental Disorders-IV criteria for major depressive disorder who were treated with at least two courses of a single antidepressant, but who had Hamilton Depression Rating Scale (HAMD-17) scores ≥15 points that were reduced less than 50% over at least a 4-week treatment period. There were 24 males and 40 females (age range 27-68 years; mean±SD, 48±13 years). The patients' clinical improvement was evaluated using the HAMD-17. Patients with at least a 50% decrease in the HAMD-17 score were defined as responders. Serum BDNF levels were assayed using enzyme-linked immunosorbent assays and the presence of the BDNF (Val66Met) polymorphism was determined using the TaqMan genotyping assay.

Results: No correlation was found between the BDNF (Val66Met) polymorphism and a positive response to adding an atypical antipsychotic drug. No differences were observed in the changes in the serum BDNF levels and HAMD-17 scores between Val66Val and Met-carriers. In addition, in patients who experienced remission, the atypical antipsychotic drug was discontinued after at least 3 months of treatment and the patients were then followed for 1 year; 14 of 27 patients (52%) relapsed within 1 year.

Conclusion: These results suggest that the BDNF (Val66Met) polymorphism is not associated with the response to the augmentation of a SSRI or SNRI with an atypical antipsychotic drug, and that the combination of an atypical antipsychotic drug and a SSRI or SNRI should be continued for 3 months or more in refractory depressed patients in the Japanese population.
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http://dx.doi.org/10.9758/cpn.2012.10.1.49DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3569156PMC
April 2012

Serum concentration of fentanyl during conversion from intravenous to transdermal administration to patients with chronic cancer pain.

Clin J Pain 2013 Jun;29(6):487-91

Department of Clinical Oncology, Aichi Cancer Center Hospital, Aichi, Japan.

Background: To the best of our knowledge, there have been no reports on the pharmacokinetics and pharmacodynamics during the conversion from continuous intravenous infusion (CII) to transdermal fentanyl administration. The primary objective of the present study was to clarify the pharmacokinetic characteristics during this conversion. A secondary objective was to identify an association between serum albumin and the absorption of fentanyl from the transdermal patch.

Methods: A prospective study was conducted from February 2010 to August 2011 that enrolled 19 patients with chronic cancer pain. Patients were classified into 2 study groups according to body mass index and albumin level. All patients received the conversion from CII to transdermal fentanyl using a 2-step taper of CII over 6 hours. Comparisons of efficacy, toxicity, and serum fentanyl concentrations between study groups were analyzed at baseline, 3, 6, 9, 12, 15, 18, and 24 hours after initiation of the conversion.

Results: The dose-adjusted serum fentanyl concentrations for all patients were significantly decreased at 15 to 24 hours after conversion compared with baseline, although pain intensity and the number of rescue events remained stable during the conversion. The dose-adjusted serum fentanyl concentrations at 9 to 24 hours were significantly reduced in the low albumin group compared with the normal albumin group (P<0.05).

Conclusions: Our study demonstrated that the dose-adjusted serum fentanyl concentrations remained relatively stable, and pain intensity and the number of rescue events remained stable during conversion. Hypoalbuminemia was strongly associated with poor absorption of transdermally administered fentanyl.
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http://dx.doi.org/10.1097/AJP.0b013e318266f6a5DOI Listing
June 2013

Serum levels of brain-derived neurotrophic factor (BDNF), BDNF gene Val66Met polymorphism, or plasma catecholamine metabolites, and response to mirtazapine in Japanese patients with major depressive disorder (MDD).

CNS Spectr 2012 Sep 10;17(3):155-63. Epub 2012 Aug 10.

Department of Psychiatry, University of Occupational and Environmental Health, Kitakyushu, Japan.

Object: We investigated an association between the polymorphism of brain-derived neurotrophic factor (BDNF) gene Val66Met and the response to mirtazapine in Japanese patients with major depressive disorder (MDD). We also examined mirtazapine's effects on the serum BDNF and plasma levels of catecholamine metabolites in these patients.

Methods: Eighty-four patients who met the DSM-IV-TR criteria for MDD were treated with only mirtazapine for 4 weeks. The BDNF Val66Met polymorphism was detected by direct sequencing in the region, and serum BDNF levels and plasma levels of catecholamine metabolites were measured by ELISA and HPLC-ECD, respectively.

Results: Mirtazapine treatment for 4 weeks significantly increased serum BDNF levels in the responders, whereas nonresponders showed significant decreases. No association was found between either of the two genotypes (Val/Val vs. Met-carriers) and the response to mirtazapine at T4 or the serum BDNF levels at T0. Mirtazapine did not alter the plasma levels of homovanillic acid (HVA) or 3-methoxy-4-hydroxyphenylglycol (MHPG). Discussion The dynamics of serum BDNF levels, but not plasma levels of HVA and MHPG, reflect the response to mirtazapine treatment; the BDNF Val66Met polymorphism in patients with depression is, however, associated with neither a particular response to mirtazapine treatment nor baseline serum BDNF levels.

Conclusion: Serum BDNF levels, but not plasma levels of HVA or MHPG, and BDNF Val66Met polymorphism are related to the mirtazapine response in MDD.
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http://dx.doi.org/10.1017/S109285291200051XDOI Listing
September 2012

Lessons learned from the Great East Japan Earthquake: impact on child and adolescent health.

Asia Pac J Public Health 2012 Jul 18;24(4):681-8. Epub 2012 Jul 18.

National Institute of Public Health, Saitama Prefecture, Japan.

The Great East Japan Earthquake (the Tohoku Earthquake) was one of the most devastating natural disasters ever to hit Japan, and its social impact was so enormous that Japan may never be the same again. This was an unprecedented triple disaster: an earthquake followed by a devastating tsunami and, finally, the destruction of a major nuclear power plant with the leaking of large amounts of radiation. The destruction occurred despite the presence of a 10-m protection wall and the effects of the tsunami were seen as high as 40 m above sea level. About 78,000 residents from areas within a 20-km radius of the Fukushima Daiichi Nuclear Power Plant were evacuated together with another 10,000 residents from areas with elevated levels of radiation. In the afflicted area, 30% of the population was older than 60 years of age, but more than 60% of the deaths were in this age cohort. Children and adolescents younger than 19 years accounted for 6.5% of the deaths, and there were 229 survivors younger than 18 years who lost both their parents in the disaster and 1295 who lost one of their parents. The long-term psychological effects on children and adolescents remain uncertain.
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http://dx.doi.org/10.1177/1010539512453255DOI Listing
July 2012

Unhealthy lifestyle, poor mental health, and its correlation among adolescents: a nationwide cross-sectional survey.

Asia Pac J Public Health 2015 Mar 18;27(2):NP1557-65. Epub 2012 Jul 18.

National Institute of Public Health, Saitama, Japan.

Objectives: The objective was to study the relationship between mental health and lifestyles of adolescents using samples representative of Japanese adolescents nationwide.

Method: The survey was conducted between December 2004 and January 2005 among students enrolled in randomly selected junior and senior high schools. Self-administered questionnaires addressed lifestyles, sleeping habits, and mental health status. Of 103 650 questionnaires collected, 85 158 were analyzed.

Results: Population characteristics associated with poor mental health were being female, being a senior high school student, skipping breakfast, not participating in extracurricular activities, not consulting parents about personal matters, parental smoking, students' smoking or alcohol use, poor subjective sleep assessment, and short or long sleeping duration.

Conclusion: Smoking and anxiety disorders are associated with an elevation in acculturative stress in adolescents. Prepossessing adolescents are in subclinical depression. Results suggest that lifestyles approaches in preventions that target students can be effective in reaching high-risk populations.
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http://dx.doi.org/10.1177/1010539512452753DOI Listing
March 2015

A novel function of the cell polarity-regulating kinase PAR-1/MARK in dendritic spines.

Bioarchitecture 2011 Nov;1(6):261-266

Department of Molecular Biology; Yokohama City University Graduate School of Medical Science; Yokohama, Japan.

Dendritic spines are postsynaptic structures that receive excitatory synaptic signals from presynaptic terminals in neurons. Because the morphology of spines has been considered to be a crucial factor for the efficiency of synaptic transmission, understanding the mechanisms regulating their morphology is important for neuroscience. Actin filaments and their regulatory proteins are known to actively maintain spine morphology; recent studies have also shown an essential role of microtubules (MTs). Live imaging of the plus-ends of MTs in mature neurons revealed that MTs stochastically enter spines and mediate accumulation of p140Cap, which regulates reorganization of actin filaments. However, the molecular mechanism by which MT dynamics is controlled has remained largely unknown. A cell polarity-regulating serine/threonine kinase, partitioning-defective 1 (PAR-1), phosphorylates classical MAPs and inhibits their binding to MTs. Because the interaction of MAPs with MTs can decrease MT dynamic instability, PAR-1 is supposed to activate MT dynamics through its MAP/MT affinity-regulating kinase (MARK) activity, although there is not yet any direct evidence for this. Here, we review recent findings on the localization of PAR-1b in the dendrites of mouse hippocampal neurons, and its novel function in the maintenance of mature spine morphology by regulating MT dynamics.
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http://dx.doi.org/10.4161/bioa.1.6.19199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3337127PMC
November 2011

Six-month treatment with atypical antipsychotic drugs decreased frontal-lobe levels of glutamate plus glutamine in early-stage first-episode schizophrenia.

Neuropsychiatr Dis Treat 2012 3;8:119-22. Epub 2012 Apr 3.

Department of Psychiatry, University of Occupational and Environmental Health, Kitakyushu, Fukuoka, Japan.

Objective: To study the effects of treatment with atypical antipsychotic drugs on brain levels of glutamate plus glutamine in early-stage first-episode schizophrenia.

Participants: Sixteen patients (eight males, eight females; aged 30 ± 11 years) completed the study.

Methods: We used administered 6 months of atypical antipsychotic drugs and used proton magnetic resonance spectroscopy to evaluate the results.

Results: We found that the administration of atypical antipsychotic drugs for 6 months decreased the glutamate plus glutamine/creatine ratio in the frontal lobe. These results suggest that the administration of atypical antipsychotic drugs for at least 6 months decreased glutamatergic neurotransmissions in the frontal lobe in early-stage first-episode schizophrenia, but there was no difference in frontal-lobe levels between patients and control subjects before administration.

Conclusion: Taking these findings into account, the glutamatergic and GABAergic neurons are implicated in early-stage first-episode schizophrenia, but in complex ways.
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http://dx.doi.org/10.2147/NDT.S25582DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3333782PMC
August 2012

The cognitive profile of aripiprazole differs from that of other atypical antipsychotics in schizophrenia patients.

J Psychiatr Res 2012 Jun 29;46(6):757-61. Epub 2012 Mar 29.

Department of Psychiatry, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, Fukuoka 8078555, Japan.

We investigated the effects of the atypical antipsychotics risperidone, olanzapine, and aripiprazole on the cognitive functions of Japanese patients with schizophrenia with respect to dosage amounts and dosing schedules. We performed a cross-sectional survey using the Brief Assessment of Cognition in Schizophrenia - Japanese Language Version (BACS-J) to evaluate the neurocognitive functions of 101 schizophrenic patients who took the same dose of one of the three aforementioned antipsychotics for at least 3 months. The BACS-J composite score correlated negatively with the prescribed dosages of risperidone and olanzapine. In contrast, we did not find a correlation between the BACS-J composite score and the prescribed dosage of aripiprazole. Moreover, the primary scores for verbal learning, motor function, and attention and processing speed were significantly lower among the patients who were taking the prescribed dosage of risperidone. The scores for verbal learning and motor function were also significantly lower when correlated with the prescribed dosage of olanzapine. We did not find a correlation between any of the primary scores on the BACS-J and the prescribed dosage of aripiprazole. In fact, the results suggest there is no linear relationship between the dose of aripiprazole and cognitive impairment, which may be due to its unique pharmacological profile.
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http://dx.doi.org/10.1016/j.jpsychires.2012.02.013DOI Listing
June 2012
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